We intend to define the sequence of human Alpha- and Beta-spectrin mRNAs and characterize the human spectrin genes. Subsequently we shall compare the structure of the spectrin genes from normal individuals and patients with inherited hemolytic anemias in order to identify whether the spectrin gene is altered in such disease. A cloned human Alpha-spectrin cDNA has recently been characterized using a mouse Alpha-spectrin cDNA which had been isolated from a bacterial expression library containing cDNAs from mouse anemic spleen. The same approach will be used to identify a human Beta-spectrin cDNA. From the human cDNAs, full length cDNAs and genomic DNA will be isolated and characterized by restriction site analysis and nucleotide sequencing. With this information, DNA and when possible RNA from patients with inherited hemolytic anemias, particularly those cases where existing evidence implicates spectrin as the site of the defect, will be analyzed in order to identify the genetic basis of these inherited diseases.